Breast cancer survivors who struggled with memory and focus after treatment said their thinking felt clearer after eight weeks of taking a supplement called oxaloacetate, in a small study led by researchers at UCLA Health1. The results were published in the journal JCO Oncology Advances1. But every woman in the study took the supplement, and there was no placebo (dummy pill) group to compare against, so the study cannot show whether oxaloacetate caused the change1.
What happened
The study enrolled 18 women with early-stage breast cancer who were between one and five years from diagnosis and reported significant thinking problems1. This kind of trouble, with memory, concentration and mental energy, is often called “chemo brain” or “brain fog,” and doctors call it cancer-related cognitive impairment1. To join, women had to score below a set cutoff on a standard questionnaire, a level read as moderately severe impairment2.
The women took 500 milligrams of oxaloacetate twice a day for eight weeks1. Oxaloacetate is a molecule the body makes on its own, and it helps cells produce energy1. Sixteen of the 18 women finished the eight weeks, and all 16 reported significant improvements in their thinking symptoms1.
The study was a Phase II trial, a mid-stage test, with a “single-arm” design, meaning everyone got the same treatment2. The women also knew what they were taking.
The evidence so far
The main measure was a questionnaire on how much trouble people felt they had with their thinking. On average, scores rose from 29.1 before treatment to 55.5 after eight weeks, which moved the group from a range considered impaired to one considered normal1. Higher scores mean fewer problems on this scale. Changes showed up after four weeks and generally grew by the end1.
The researchers also reported:
- significant drops in overall fatigue and in mental fatigue3;
- better physical functioning3;
- better results on standard thinking tests of executive function (planning, focusing and managing tasks) and processing speed1.
The lead researcher also said sleep problems improved4. Most of the women had had chemotherapy (61%), and 89% were taking endocrine (hormone-blocking) therapy during the study3. Their average age was 49.65.
The team first planned to check the results after nine people, counting it a positive sign if the main score rose by 4 points. The early analysis showed a 27-point rise2. “The impressive and universal improvements in perceived cognitive impairment in the first nine study participants encouraged us to redesign the study to be able to complete it with a smaller total sample size and to hasten the development of a randomised, placebo-controlled trial,” the authors wrote2.
The supplement was generally well tolerated1. The most common side effects were indigestion, bloating, constipation, diarrhea and nausea, and two women stopped because of these gut problems1. No serious side effects were reported1.
What it does not show yet
The biggest gap is the missing comparison group. The researchers themselves caution that the study was small and had no placebo or comparison group, so more research is needed to find out whether oxaloacetate was responsible for the improvements1. Without a dummy-pill group, the changes could also come from other things, such as people expecting to feel better or symptoms easing over time. Most of the main results were also based on how people rated themselves, and the researchers called the thinking-test results preliminary because the study was so small1.
Doctors quoted about the study were cautious. Larry Norton, a breast cancer doctor at Memorial Sloan Kettering who was not an author, said possible side effects of oxaloacetate have not been fully explored4:
“All medicines have good and not-so-good effects. For this reason, it is important to follow the well-established processes that determine if the balance of good outweighs the downsides. This has not yet been accomplished with this compound.”
Norton also said several fixable problems, such as anemia, sleep problems, depression and thyroid function, can be mistaken for drug-related mental changes, so the evaluation of “fog” needs to be thorough4. He added that most treatment-related changes in thinking are mild and short-lived, and that fear of them is not a good reason to avoid potentially lifesaving cancer drugs4.
The lead author, Patricia Ganz, said: “Right now, we cannot recommend this supplement without future testing, but it is very encouraging to know that there is a medication that can reverse these bothersome post-treatment symptoms”4. Halle Moore of the Cleveland Clinic, who was not involved, called the results impressive despite the small size and lack of a control group, and said “the main point is that it supports proceeding to a longer randomised trial where we would compare to a control group”2.
Who is behind it
The study was led by Ganz, a distinguished professor of medicine at UCLA, through the UCLA Health Jonsson Comprehensive Cancer Center1. It was funded in part by the Breast Cancer Research Foundation and the National Cancer Institute1. Ganz is also a Breast Cancer Research Foundation investigator, and the foundation published its own article on the results5. Most of the detailed figures in this story come from UCLA’s announcement and from coverage of the paper; Biohack did not read the full paper. The sources do not say who supplied the supplement.
How it fits the field
Estimates of how common lasting brain fog is differ a little between the sources. UCLA’s announcement says 15% to 25% of breast cancer survivors1, Ganz told Prevention 20% to 25%4, and she gave a figure of about 25% to the Breast Cancer Research Foundation5. There are no medicines designed to treat it, Ganz said4.
Brain fog after cancer was long linked mainly to chemotherapy, but researchers now think the causes are more complex and may include the cancer itself, hormone therapy, inflammation and other factors1. The researchers’ idea is that inflammation may disturb glutamate, a brain signaling chemical involved in learning and memory, and the way brain cells make energy; oxaloacetate plays a role in both1. That explanation has not been confirmed4.
Most earlier research on this problem has tested approaches such as exercise and managing anxiety and depression, Moore said2. One example is a University of Missouri study, still recruiting, that is testing a thinking-strategies training program against an inactive control group in about 50 breast cancer survivors6. Oxaloacetate has also drawn interest for long COVID: a small randomized study in people with long COVID symptoms reported better thinking performance with the supplement2.
What to watch next
The team is preparing a randomized trial that compares oxaloacetate with a placebo in breast cancer survivors with brain fog1. The Breast Cancer Research Foundation says the US Food and Drug Administration has cleared that trial to go ahead5. UCLA says it is expected to open in late 20261, and coverage reported enrollment should start before year-end2. Studies in mice, including a placebo-controlled one, are also under way to learn how oxaloacetate might act1.
That trial is the real test. If women on oxaloacetate do better than women on a dummy pill, the result would say much more than this study can. If both groups improve about equally, the gains seen here may have had other causes.
